WEBVTT - Ep 101 Immortality: This Podcast Won't Kill You 0:00:02.080 --> 0:00:06.160 Hi everyone. Aaron here you are about to listen to 0:00:06.360 --> 0:00:11.719 a very exciting episode on immortality. And this episode is 0:00:11.800 --> 0:00:15.720 not just exciting because of the topic, but also because 0:00:15.920 --> 0:00:19.680 it was going to be our one hundredth regular season episode. 0:00:20.360 --> 0:00:23.599 But when things with monkeypox started to ramp up, we 0:00:23.720 --> 0:00:26.040 decided that we wanted to make sure that we got 0:00:26.079 --> 0:00:29.560 a monkey pox's episode out to you as quickly as possible, 0:00:30.160 --> 0:00:33.400 and that meant pushing back this immortality episode, which we 0:00:33.440 --> 0:00:38.400 had actually recorded before monkey pocks. So throughout this episode 0:00:38.560 --> 0:00:42.600 you may hear references to this being our one hundredth episode, 0:00:43.080 --> 0:00:46.519 even though it's actually episode one hundred and one, and 0:00:46.560 --> 0:00:50.239 we just wanted to explain why in advance. Okay, I 0:00:50.320 --> 0:00:55.560 think that about covers it, So let's get started introducing immortality. 0:00:58.160 --> 0:01:01.160 The life that you seek you never will find. When 0:01:01.200 --> 0:01:05.840 the gods created mankind death, they dispensed to mankind life 0:01:06.080 --> 0:01:10.440 they kept for themselves. But you, Gilgamesh, Let your belly 0:01:10.480 --> 0:01:13.840 be full, enjoy yourself always by day and by night. 0:01:14.440 --> 0:01:17.840 Make mary each day, dance and play day and night. 0:01:18.480 --> 0:01:21.320 Let your clothes be clean, Let your head be washed. 0:01:21.640 --> 0:01:24.560 May you bathe in water. Gaze on the child who 0:01:24.560 --> 0:01:28.319 holds your hand. Let your wife enjoy your repeated embrace. 0:02:14.400 --> 0:02:19.200 I still don't actually know the story of Gilgamesh. 0:02:19.360 --> 0:02:22.680 I still only know a little part of the story 0:02:22.720 --> 0:02:29.040 of Gilgamesh. So yes, that was from the epic of Gilgamesh, 0:02:29.080 --> 0:02:32.160 which is one of the oldest I think actually the 0:02:32.560 --> 0:02:37.240 considered the oldest like surviving document or text. 0:02:37.680 --> 0:02:39.240 Wow, that's amazing. 0:02:39.560 --> 0:02:43.720 Yeah, yeah, it's from a long time ago, like two 0:02:43.760 --> 0:02:45.880 thousand BCE something like that. 0:02:46.040 --> 0:02:46.639 Wow. 0:02:47.320 --> 0:02:51.519 Yeah. Hi, I'm Aaron Welsh. 0:02:50.919 --> 0:02:53.120 And I'm Aaron Allman Updike. 0:02:53.200 --> 0:02:55.400 And this is this podcast will kill you. 0:02:55.720 --> 0:02:58.480 And today we're not just like reading you the story 0:02:58.480 --> 0:03:00.239 of Gilgamesh. 0:03:00.240 --> 0:03:05.600 That's most of what you'll hear about Yogamesh. 0:03:05.680 --> 0:03:09.360 Today, we're doing something very different in honor of our 0:03:09.760 --> 0:03:11.400 one hundredth episode. 0:03:11.680 --> 0:03:15.600 One hundredth I mean it is. I can't believe it. 0:03:15.880 --> 0:03:18.160 I never would have thought we could make one hundred 0:03:18.200 --> 0:03:20.959 episodes of a podcast, Darin either. 0:03:21.160 --> 0:03:24.119 And Okay, here's the thing is that, like technically we 0:03:24.200 --> 0:03:27.119 surpassed one hundred a long time. 0:03:27.200 --> 0:03:29.320 That's true. I forgot about that with. 0:03:29.240 --> 0:03:32.120 Like all the COVID episodes and all the bonus one 0:03:32.200 --> 0:03:36.920 bonus episodes. Yeah, still, this is this is our like 0:03:37.000 --> 0:03:40.680 our title episode one hundred, Yeah, and I think in 0:03:40.800 --> 0:03:44.000 honor of that, as we slowly get around to talking 0:03:44.040 --> 0:03:48.400 about what we're going to be talking about today, we 0:03:48.480 --> 0:03:51.720 thought it would be fun to take the name of 0:03:51.720 --> 0:03:54.600 our podcast and change it up a bit, right, this 0:03:54.720 --> 0:03:57.200 podcast will kill you today. 0:03:57.760 --> 0:04:03.000 This podcast won't kill you. Yeah, it might make you 0:04:03.120 --> 0:04:08.200 live forever, probably not give you the secrets to eternal life. 0:04:09.080 --> 0:04:13.000 Today, we're going to be talking about immortality and aging. 0:04:13.200 --> 0:04:17.320 And it's definitely not going to be a comprehensive journey 0:04:17.480 --> 0:04:22.200 through the history of aging and how immortality could be achieved, 0:04:22.720 --> 0:04:25.120 but I think it's going to be a nice little taste. 0:04:25.160 --> 0:04:27.560 Yeah, And our structure is going to be a little 0:04:27.560 --> 0:04:31.520 different than usual because it's such an amorphist topic. Yeah. 0:04:31.560 --> 0:04:34.280 So I'm going to be starting out talking about the 0:04:34.400 --> 0:04:39.000 history of immortality and what that means in terms of evolution, 0:04:39.240 --> 0:04:42.200 and then what that means in terms of like human culture, 0:04:42.279 --> 0:04:44.640 and again it's just sort of like a brief, little 0:04:44.720 --> 0:04:46.880 jump through, yeah topic. 0:04:46.920 --> 0:04:49.640 And then I'm going to talk about I don't really 0:04:49.760 --> 0:04:56.200 know what erin maybe like where we stand in terms 0:04:56.279 --> 0:05:00.720 of like aging today or anti aging research or the 0:05:00.880 --> 0:05:04.600 quest for immortality, what we know about the biology of it. 0:05:04.760 --> 0:05:05.120 I don't know. 0:05:05.200 --> 0:05:07.800 It's going to be a little bit of a conversation. 0:05:08.279 --> 0:05:11.880 I think it's going to be really exciting and fun. Yeah, 0:05:12.080 --> 0:05:13.040 I'm just looking. 0:05:12.760 --> 0:05:15.840 Forward to us same same Well, speaking of like. 0:05:15.920 --> 0:05:18.760 Tastes of things. What time is it? 0:05:18.839 --> 0:05:22.960 Oh, quarantiny time still is quarantiny time. 0:05:22.960 --> 0:05:27.119 Still is always quarantiny time. What are we drinking this week? 0:05:27.240 --> 0:05:30.120 Well, of course we're drinking none other than the Elixir 0:05:30.200 --> 0:05:30.920 of Life. 0:05:31.080 --> 0:05:35.400 We are and in the Elixir of Life. It's a 0:05:35.800 --> 0:05:38.520 it's a fun little it's a fun little drink because 0:05:38.720 --> 0:05:43.480 we've got gin, we've got lemon juice, we've got blackberries, 0:05:43.520 --> 0:05:46.680 we've got simple syrup. And then to kind of like 0:05:46.839 --> 0:05:51.720 create the fun little magical I don't know aura around it, 0:05:52.200 --> 0:05:56.240 we've got butterfly pea flower extract, which was sent to 0:05:56.320 --> 0:06:00.360 us by a very generous listener, so thank you so much. 0:06:00.520 --> 0:06:02.720 It is such a cool looking drink. 0:06:03.320 --> 0:06:05.719 It's a nice I'm really excited about. I want to 0:06:05.720 --> 0:06:08.560 come visit you so that I can actually taste it. 0:06:09.640 --> 0:06:14.039 Okay, let's make that happen. Yeah, we will post the 0:06:14.120 --> 0:06:17.680 full recipe for the Elixir of Life as well. As 0:06:17.720 --> 0:06:20.880 the non alcoholic place Rita on our website This podcast 0:06:20.960 --> 0:06:23.400 will kill You dot Com, as well as on all 0:06:23.400 --> 0:06:25.360 of our social media channels. 0:06:25.360 --> 0:06:27.960 Our website This podcast will kill You dot Com. If 0:06:28.000 --> 0:06:29.960 you haven't been there yet, you should go and check 0:06:30.000 --> 0:06:34.360 it out. After one hundred episodes, try it. We have 0:06:34.600 --> 0:06:37.960 merch we have transcripts. We have links to our bookshop 0:06:37.960 --> 0:06:42.440 dot org affiliate account. We have links to our music bloodmobile. 0:06:42.920 --> 0:06:46.120 We have a good Reads list, we have all of 0:06:46.160 --> 0:06:49.160 our sources for all of our episodes. We have our Patreon. 0:06:49.320 --> 0:06:52.960 We have more than I could say in that single breath. 0:06:53.160 --> 0:06:55.440 Well, I think you did a great job. Thanks, loving 0:06:55.480 --> 0:06:57.520 all right, any other business? 0:06:57.760 --> 0:07:01.279 No, Aaron, please tell me, like I don't know, from 0:07:01.320 --> 0:07:06.120 Gilgamesh to now, how has humanity fared on our quest 0:07:06.120 --> 0:07:06.960 for immortality? 0:07:07.800 --> 0:07:11.000 Great questions there I will, I will do my very 0:07:11.000 --> 0:07:45.720 best right after this break. Like we said, this is 0:07:46.080 --> 0:07:50.080 definitely not our typical format. But then again, this is 0:07:50.240 --> 0:07:54.360 not our typical episode topic. So the focus of our 0:07:54.400 --> 0:07:59.600 episode today is immortality. But what does that mean? Not 0:07:59.840 --> 0:08:02.040 just like what are we going to cover, but the 0:08:02.080 --> 0:08:07.560 word or the concept itself is immortality, simply living forever, 0:08:08.440 --> 0:08:13.480 not aging, being invulnerable to any illness or injury. Does 0:08:13.520 --> 0:08:15.880 it mean that your name and life will be remembered 0:08:16.040 --> 0:08:19.360 hundreds of years from now, or that your genes will 0:08:19.400 --> 0:08:22.320 be carried on in your offspring and their offspring, and 0:08:22.360 --> 0:08:25.240 so on and so on down the line. There are 0:08:25.280 --> 0:08:28.440 many different ways that we can think of and have 0:08:28.640 --> 0:08:32.880 thought of immortality. And if your goal is to achieve immortality, 0:08:33.160 --> 0:08:37.720 which definition you choose has tremendous bearing on how you 0:08:37.760 --> 0:08:40.440 go about that, And that can also be said for 0:08:40.480 --> 0:08:46.839 this episode. So how will we consider immortality today? Really, 0:08:46.880 --> 0:08:49.800 we'll at least touch on the most common concepts in 0:08:49.800 --> 0:08:54.680 a general sense, but since we're a health and science podcast, 0:08:55.160 --> 0:08:57.840 most of what we'll talk about is immortality from a 0:08:57.880 --> 0:09:03.360 biological perspective. First by talking about not what immortality is 0:09:03.559 --> 0:09:06.839 and how we can achieve it, but what stops us 0:09:06.880 --> 0:09:10.960 from being immortal in the first place? Why do we die? 0:09:11.800 --> 0:09:15.080 Why do we decline as we get older? Are there 0:09:15.120 --> 0:09:18.880 any organisms that don't? What do we know or think 0:09:18.920 --> 0:09:23.640 about senescence, the decline or deterioration we experience as we 0:09:23.720 --> 0:09:28.280 age from an evolutionary perspective, And then all turn from 0:09:28.480 --> 0:09:32.120 that to talking about the age long quest for immortality, 0:09:32.600 --> 0:09:36.560 which has roots much much older than these startups in 0:09:36.760 --> 0:09:39.800 Silicon Valley that have been looking for modern elixirs of 0:09:39.840 --> 0:09:41.520 life that I know you're going to be talking a 0:09:41.520 --> 0:09:45.720 bit more about, Aaron Yeap. What patterns do we see 0:09:45.840 --> 0:09:49.720 in the different ways that people have approached immortality through history? 0:09:50.360 --> 0:09:53.640 And how has this past century and our ever growing 0:09:53.720 --> 0:09:59.280 understanding of biology changed the targets for immortality research. And 0:09:59.280 --> 0:10:00.760 then that's sort of where I'll hands it off to 0:10:00.800 --> 0:10:03.600 you Erin to tell us how close we are or 0:10:03.760 --> 0:10:08.240 probably aren't to achieving immortality and the nitty gritty of 0:10:08.280 --> 0:10:12.040 what people are working on. Okay, okay, all right, so 0:10:12.320 --> 0:10:16.880 let's get into it. Living things age, but they don't 0:10:16.920 --> 0:10:20.680 just experience the passage of time. They also change as 0:10:20.720 --> 0:10:24.720 time passes, first growing and developing, and then at a 0:10:24.760 --> 0:10:28.200 certain point that growth ceases and a new kind of 0:10:28.280 --> 0:10:32.360 change occurs, one where maybe things don't heal quite as 0:10:32.360 --> 0:10:35.680 fast as they used to, or those aches and pains 0:10:35.720 --> 0:10:40.800 get more frequent, and eventually recovery is no longer a possibility, 0:10:41.400 --> 0:10:45.240 with death being the ultimate end. And this is generally 0:10:45.280 --> 0:10:49.360 how it happens for every living thing. And sure, the 0:10:49.400 --> 0:10:51.920 amount of time that you spend in each life stage 0:10:52.000 --> 0:10:54.760 may be different, or how long you can expect to 0:10:54.800 --> 0:10:59.240 live will vary, but death and aging are essential parts 0:10:59.400 --> 0:11:03.480 of life, even for those supposedly immortal animals that you 0:11:03.559 --> 0:11:06.959 see like click bait headlines about like lobsters or certain 0:11:07.000 --> 0:11:12.800 jellyfish or bristle cone pines. But while senescence, the biological 0:11:12.880 --> 0:11:17.079 decline part of aging may not be as marked as 0:11:17.120 --> 0:11:21.600 in other creatures, those organisms are not truly immortal. They 0:11:21.720 --> 0:11:27.000 will die eventually because nothing living is immune to death. 0:11:28.480 --> 0:11:31.400 Why does this have to happen? Like, why can't we 0:11:31.440 --> 0:11:34.800 go on living forever? Well, let's think about it in 0:11:34.840 --> 0:11:38.120 the context of natural selection and evolutionary fitness. 0:11:38.720 --> 0:11:39.480 That's arh. 0:11:40.920 --> 0:11:44.520 Evolutionary fitness, for those who haven't heard the term before, 0:11:45.160 --> 0:11:50.480 is essentially an individual's reproductive success how many offspring they have. 0:11:51.440 --> 0:11:55.760 If an individual has no offspring, zero fitness. If they 0:11:55.840 --> 0:11:59.760 don't survive long enough to reproduce, fitness is also zero. 0:12:00.559 --> 0:12:03.559 But the individuals who do live long enough to reproduce 0:12:03.679 --> 0:12:06.240 and have a lot of offspring, those are the ones 0:12:06.280 --> 0:12:08.240 who are going to contribute the most to the next 0:12:08.280 --> 0:12:12.920 generation's gene pool. Traits that limit your ability to reproduce 0:12:13.120 --> 0:12:17.640 or survive through reproductive age. Those traits lower your fitness 0:12:17.760 --> 0:12:20.000 and make it less likely for those genes to be 0:12:20.040 --> 0:12:24.160 passed on to the next generation. And over time those 0:12:24.280 --> 0:12:28.400 traits those genes will become less and less common, maybe 0:12:28.520 --> 0:12:32.040 eventually disappearing. But traits that make you more likely to 0:12:32.080 --> 0:12:36.000 reproduce or survive through the end of reproductive age, those 0:12:36.040 --> 0:12:38.040 are the traits that are going to be selected for 0:12:38.360 --> 0:12:41.800 becoming more common. So we can think of tons of 0:12:41.840 --> 0:12:45.600 examples of this, right, like the size of a bird's beak, 0:12:46.000 --> 0:12:50.520 or the rate of development of a tadpole into a frog, 0:12:51.240 --> 0:12:55.880 or fur pattern or susceptibility to disease. But what's so 0:12:56.040 --> 0:13:00.720 crucial about this for this discussion is not the trait themselves, 0:13:00.760 --> 0:13:04.800 not these examples, but rather the time window when these 0:13:04.840 --> 0:13:09.240 traits matter most, and that is the critical period from 0:13:09.280 --> 0:13:12.880 basically prenatal development all the way through the end of 0:13:12.960 --> 0:13:16.400 when you are able to reproduce. That is when selection 0:13:16.520 --> 0:13:21.280 can act. With this in mind, what does it matter 0:13:21.679 --> 0:13:25.199 really in terms of natural selection if you live past 0:13:25.280 --> 0:13:27.880 reproductive age. It doesn't. 0:13:28.280 --> 0:13:29.199 It doesn't at all. 0:13:29.280 --> 0:13:32.520 It doesn't. Yeah, if there are genes that affect at 0:13:32.600 --> 0:13:36.600 least in part your longevity. How will natural selection act 0:13:36.640 --> 0:13:38.679 on them if they don't have any bearing on your 0:13:38.720 --> 0:13:43.360 reproductive fitness. It won't, It won't, I mean, And there 0:13:43.440 --> 0:13:49.080 are genes in humans that are associated with longevity, but 0:13:49.120 --> 0:13:52.720 it's likely that those play a role in maintenance or development, 0:13:53.120 --> 0:13:58.120 and they don't just switch on later in life exactly. Yeah. 0:13:58.160 --> 0:14:01.160 So essentially, in terms of natural select it doesn't really 0:14:01.200 --> 0:14:04.040 matter how long we live past the point when we're 0:14:04.040 --> 0:14:09.520 no longer reproductively viable. And this is of course like 0:14:10.280 --> 0:14:14.679 a big oversimplification, and for humans and other animals, there 0:14:14.720 --> 0:14:19.880 are some very interesting hypotheses about why we humans live 0:14:20.000 --> 0:14:24.240 long past the age we reproduce, mostly centering around grandparents, 0:14:24.280 --> 0:14:26.960 and I'd love to get into that one day with 0:14:27.040 --> 0:14:28.840 an episode on menopause. Oh. 0:14:29.000 --> 0:14:31.400 I we'll definitely do it on menopause because I love 0:14:31.560 --> 0:14:36.440 all of the evolutionary theories behind menopause and just like aging, 0:14:36.640 --> 0:14:37.840 and like the grandparents. 0:14:37.920 --> 0:14:41.400 Oh, I love the grandparent hypothesis. Oh it's so interesting. 0:14:41.520 --> 0:14:42.240 Yeah, I love it. 0:14:43.440 --> 0:14:47.280 But anyway, we humans are not unique in that we 0:14:47.320 --> 0:14:50.400 live past the age we reproduce, nor are we unique 0:14:50.440 --> 0:14:52.840 in the fact that our bodies and minds start to 0:14:52.880 --> 0:14:57.120 deteriorate as we get older. And even if life past 0:14:57.200 --> 0:15:01.320 reproduction is not part of natural selection, what makes us 0:15:01.360 --> 0:15:06.400 and other organisms age? Like? Why do we age? And 0:15:06.440 --> 0:15:11.040 we have been asking ourselves this question, probably since we 0:15:11.040 --> 0:15:15.160 were able to form thought, but it wasn't until Charles 0:15:15.240 --> 0:15:18.720 Darwin introduced the theory of evolution by natural selection in 0:15:18.720 --> 0:15:22.720 the mid nineteenth century that people had a scientific framework 0:15:22.760 --> 0:15:25.120 that they could use to try to answer this question. 0:15:26.040 --> 0:15:29.880 Since that time, many different hypotheses have been proposed, none 0:15:29.920 --> 0:15:34.000 of which seem to adequately explain sinessence for every living thing. 0:15:34.760 --> 0:15:37.080 And I'm going to briefly go through a few of 0:15:37.120 --> 0:15:40.560 the classical hypotheses of sinessence so that we can try 0:15:40.560 --> 0:15:44.000 to think about possible mechanisms that could explain why aging 0:15:44.240 --> 0:15:49.560 is universal. The first of these hypotheses was proposed in 0:15:49.600 --> 0:15:54.360 the eighteen nineties by the German evolutionary biologist August Weismann 0:15:54.480 --> 0:15:58.960 the so called germ soma theory, and so Weisman suggested 0:15:58.960 --> 0:16:01.920 that there were two types of cell lines in an organism, 0:16:02.280 --> 0:16:05.560 a germ line and a soma or body line, and 0:16:05.600 --> 0:16:07.720 the germ line is made up of the cells that 0:16:07.760 --> 0:16:11.240 are involved in reproduction and the soma line consists of 0:16:11.280 --> 0:16:14.440 the cells that make up the rest of the body. 0:16:14.560 --> 0:16:17.720 It's the sole duty of the soma cells to do 0:16:17.920 --> 0:16:21.800 whatever it takes to keep the germ line alive and reproducing. 0:16:22.520 --> 0:16:27.080 Beyond that, soma cells basically disposable, and the soma cell 0:16:27.160 --> 0:16:30.640 lineage will invariably die, while the germ cell lineage can 0:16:30.720 --> 0:16:35.920 be viewed as potentially immortal. Aging happens as the soma 0:16:36.000 --> 0:16:38.760 line gets beat up by the environment while protecting the 0:16:38.800 --> 0:16:44.080 germ line. And that's the hypothesis. Yeah, obviously it has 0:16:44.120 --> 0:16:48.280 many shortcomings, first of them being that it doesn't really 0:16:48.400 --> 0:16:53.360 explain why sinessence evolved, like why the soma is disposable, 0:16:54.160 --> 0:16:58.440 and it doesn't explain sinessence in single celled organisms. But 0:16:58.520 --> 0:17:01.920 it did introduce the idea that reproduction is first and 0:17:02.000 --> 0:17:06.600 foremost the priority, and many later researchers built upon this idea, 0:17:06.840 --> 0:17:11.240 such as the famous mathematician and eugenicist Ronald Fisher, who 0:17:11.320 --> 0:17:14.400 in the nineteen thirties proposed a mathematical model in which 0:17:14.440 --> 0:17:17.560 he laid out his thoughts that sinessence was the accumulation 0:17:17.760 --> 0:17:21.920 of harmful age specific traits. A couple of decades later, 0:17:22.040 --> 0:17:26.040 in the nineteen fifties, Peter Medowar, whose name you might 0:17:26.240 --> 0:17:32.600 remember from our organ transplantation episode. He wrote a now 0:17:32.680 --> 0:17:36.480 famous essay describing how the force of selection weakens as 0:17:36.520 --> 0:17:40.560 we get older and past our reproductive age. He wasn't 0:17:40.720 --> 0:17:44.439 entirely right either, For instance, his belief that animals in 0:17:44.440 --> 0:17:47.600 the wild don't get old they don't siness because they 0:17:47.640 --> 0:17:50.520 just get picked off by predators or succumb to starvation. 0:17:51.160 --> 0:17:54.679 They actually do siness, they actually do get older. But 0:17:54.800 --> 0:17:58.280 his essay did suggest a sort of mechanism for Sinessence, 0:17:59.040 --> 0:18:03.119 if there are genes that do exist that shorten our lifespan, 0:18:03.400 --> 0:18:06.200 they won't really be selected against if they only show 0:18:06.200 --> 0:18:09.560 their effects later in life, and so they will continue 0:18:09.560 --> 0:18:15.040 to appear and accumulate over generations. The quote mutation accumulation theory. 0:18:15.600 --> 0:18:20.159 That's I love. Sorry, I just really do love these hypotheses. 0:18:20.440 --> 0:18:21.000 I do too. 0:18:21.320 --> 0:18:22.560 I find it really fun. 0:18:22.920 --> 0:18:25.840 It was it was so interesting because I have never 0:18:26.600 --> 0:18:29.320 even though I said, humans have probably asked themselves this 0:18:29.440 --> 0:18:33.720 question forever, and I've probably asked myself this question too, 0:18:34.040 --> 0:18:36.840 but not in like a okay, but why what is 0:18:36.880 --> 0:18:39.440 the actual evolutionary mechanism behind it? 0:18:39.840 --> 0:18:43.320 I feel like I only ever thought about another hypothesis. 0:18:43.320 --> 0:18:45.879 I think you're probably going to talk about next in 0:18:45.960 --> 0:18:48.320 the context of the evolution of human health class that 0:18:48.359 --> 0:18:51.520 I ta' for. So that was like a very specific 0:18:51.960 --> 0:18:54.159 subset of time that I was thinking about it. 0:18:54.480 --> 0:18:57.159 Yeah, it is. It's so fun to think about. Okay, 0:18:57.200 --> 0:18:58.680 so there are there are a few more. 0:18:59.040 --> 0:18:59.240 Yeah. 0:18:59.640 --> 0:19:04.159 So. Years after Metowar's essay, George Williams added on to 0:19:04.240 --> 0:19:07.920 this by suggesting that in addition to these mutations appearing, 0:19:08.440 --> 0:19:11.720 it's also possible that those genes that are helpful early 0:19:11.800 --> 0:19:15.840 in life, like in development and during reproduction, could also 0:19:15.920 --> 0:19:19.280 be bad or have negative effects later in life. Like, 0:19:19.440 --> 0:19:23.600 for instance, let's think about cell growth. If your cells 0:19:23.680 --> 0:19:28.280 grow super fast, that's potentially great when you're developing right, 0:19:28.400 --> 0:19:33.800 you get larger faster and can be independent faster. But 0:19:34.040 --> 0:19:38.840 later on that could mean uncontrolled cell growth aka cancer. 0:19:40.240 --> 0:19:40.520 Yep. 0:19:41.000 --> 0:19:43.840 And this is something that's called antagonistic pliotropy. 0:19:44.200 --> 0:19:47.000 It's one of my favorite concepts and I love it. 0:19:46.680 --> 0:19:49.520 It's so it's I mean, and it like the thing 0:19:49.640 --> 0:19:51.840 they all make sense, And the thing that I like 0:19:51.880 --> 0:19:53.800 too about them is that none of them are really 0:19:54.720 --> 0:19:56.760 mutually exclusive. 0:19:56.680 --> 0:20:00.879 Exactly like you have, you can easily we have mutations 0:20:00.880 --> 0:20:04.280 that accumulate as well as have genes that are beneficial 0:20:04.320 --> 0:20:07.320 early in life and maybe have a detriment later in life. 0:20:07.320 --> 0:20:12.120 So like these mutation, accumulation, antagonistic piotropy, these hypotheses really 0:20:12.160 --> 0:20:16.119 do work together to explain aging in a way that 0:20:16.200 --> 0:20:17.440 I think is just fascinating. 0:20:17.640 --> 0:20:22.479 Yep, yeah, exactly. And also what really helped things along 0:20:22.560 --> 0:20:26.200 in this in this field was when in nineteen sixty 0:20:26.200 --> 0:20:30.159 six William Hamilton combined some of these existing ideas on 0:20:30.400 --> 0:20:34.439 the evolution of aging into a mathematical model, which, like, 0:20:35.000 --> 0:20:38.000 maybe that doesn't sound very exciting, but it really is. 0:20:38.080 --> 0:20:41.960 It was, and it's still today is super impactful because 0:20:42.000 --> 0:20:45.320 it laid out a framework for why aging happens, and 0:20:45.400 --> 0:20:48.360 it also showed that the strength of selection on traits 0:20:48.359 --> 0:20:51.880 that keep you alive it becomes weaker over time in 0:20:51.920 --> 0:20:56.879 anything that ages and doesn't reproduce via fission. Yeah. Really, 0:20:57.000 --> 0:20:59.240 Also what it did was create a math model for 0:20:59.280 --> 0:21:02.120 people to be able to to test ideas about aging. 0:21:03.520 --> 0:21:06.639 The last of the classical hypotheses of sinessence I'm going 0:21:06.720 --> 0:21:11.240 to talk about is the quote disposable soma theory. Proposed 0:21:11.280 --> 0:21:15.040 by Thomas Kirkwood in nineteen seventy seven, which says that 0:21:15.119 --> 0:21:20.840 over time and organism cells accumulate harmful genetic mutations. Mutations 0:21:20.840 --> 0:21:24.159 in your DNA happen randomly all the time because of 0:21:24.280 --> 0:21:28.760 environmental factors or mistakes in DNA replication, and it gets 0:21:28.800 --> 0:21:32.600 increasingly costly to repair the damage from these mutations, and 0:21:32.800 --> 0:21:36.080 at a certain point, the benefit of repairing the damage 0:21:36.160 --> 0:21:40.280 is outweighed by the cost repair and maintenance is always 0:21:40.320 --> 0:21:44.359 going to favor the germline. Okay, so these are just 0:21:44.440 --> 0:21:48.280 a few of the most impactful hypotheses to explain why 0:21:48.320 --> 0:21:52.760 sinessence evolved, but there are certainly others, and no single 0:21:52.840 --> 0:21:56.119 hypothesis at this point seems to be able to explain 0:21:56.200 --> 0:22:01.680 aging for all organisms. There's no unifying hypothesis, probably because 0:22:01.840 --> 0:22:08.560 like there's tremendous diversity in life, no is there. 0:22:08.480 --> 0:22:11.159 Really are I mean that like a bristle combe pine 0:22:11.240 --> 0:22:13.120 is not the same thing as a plenariat. 0:22:13.280 --> 0:22:19.160 It might not be, and even some of the fundamental 0:22:19.160 --> 0:22:26.040 assumptions about aging have been challenged. It's an extraordinarily complicated 0:22:26.040 --> 0:22:30.320 thing to study. You have to capture both how different 0:22:30.440 --> 0:22:35.160 environments and different genes impact aging. You have to consider 0:22:35.200 --> 0:22:40.040 ecological factors, determine whether aging in the lab is different 0:22:40.160 --> 0:22:43.600 or the same as aging in the wild, evaluate whether 0:22:43.680 --> 0:22:47.720 closely related species age more similarly than distantly related ones. 0:22:48.600 --> 0:22:51.760 And the biggest thing in my eyes is that we've 0:22:51.800 --> 0:22:54.760 really only begun looking at this within the past one 0:22:54.880 --> 0:22:58.040 hundred and thirty years or so, which is shorter than 0:22:58.080 --> 0:23:01.240 the average lifespan of some organs. That could give us 0:23:01.480 --> 0:23:04.000 really valuable insight into longevity. 0:23:04.680 --> 0:23:06.520 Good point, So, like, how do you how do. 0:23:06.480 --> 0:23:10.480 You create a data set? Yeah, for giant tortoise? 0:23:11.040 --> 0:23:15.480 Right, well, even studying human aging, like we live a 0:23:15.520 --> 0:23:17.359 really long time, right, and. 0:23:17.440 --> 0:23:20.640 There have been really cool like census records and especially 0:23:20.640 --> 0:23:24.000 in certain countries or certain regions that keep really good 0:23:24.040 --> 0:23:28.680 track of like people through time, but we still don't 0:23:28.680 --> 0:23:30.520 have all the bits of information there, right. 0:23:30.760 --> 0:23:31.240 Yeah. 0:23:31.760 --> 0:23:36.280 So it's it's in a way we've been thinking about 0:23:36.320 --> 0:23:38.160 it for a long time, but it seems like we're 0:23:38.200 --> 0:23:41.920 definitely in the infancy of having data to be able 0:23:41.960 --> 0:23:43.240 to test these hypotheses. 0:23:43.520 --> 0:23:45.520 Aaron, you just summed up my whole section. 0:23:50.200 --> 0:23:53.640 It's it was it was really interesting to read through 0:23:53.680 --> 0:23:57.560 this also because I don't think I realized just how 0:23:57.880 --> 0:24:01.280 huge of a field of study this, And I guess 0:24:01.280 --> 0:24:04.320 I should have because there are like, you know, entire 0:24:04.400 --> 0:24:09.000 journals and entire textbooks at entire companies and everything, but 0:24:09.200 --> 0:24:14.639 like it is, it is really hard to do it justice. Yeah, yeah, 0:24:14.960 --> 0:24:18.199 so yeah, So I just kind of wanted to like 0:24:18.359 --> 0:24:22.080 wander through some of these ideas and kind of fell 0:24:22.480 --> 0:24:26.000 and build a baseline for thinking about aging in an 0:24:26.040 --> 0:24:29.800 evolutionary context, especially when it comes to like natural selection 0:24:30.520 --> 0:24:33.119 and wouldn't it be great if we lived forever but 0:24:33.280 --> 0:24:38.720 we don't really need to, yeah, in terms of our DNA. 0:24:38.400 --> 0:24:40.560 Getting passed on, Yeah, exactly. 0:24:40.880 --> 0:24:43.960 Yeah, And I also thought it was important to think 0:24:44.040 --> 0:24:49.520 about these things like why we age before we start 0:24:49.920 --> 0:24:53.760 exploring some of the ways that we've tried and continue 0:24:53.800 --> 0:24:59.600 to try to stop or slow that process. So, if 0:24:59.680 --> 0:25:02.920 they're there is anything that humans are good at, it's 0:25:02.960 --> 0:25:08.399 searching for the key to immortality. We're really good at 0:25:08.440 --> 0:25:12.400 searching for it, but we are terrible at finding it. Yeah, 0:25:12.480 --> 0:25:17.560 because we've not found it. Yeah, spoilers, we don't have it. Spoilers, 0:25:17.600 --> 0:25:21.280 we don't have it. We may not have it ever. 0:25:22.720 --> 0:25:28.159 Immortality narratives are central to every culture and religion, like 0:25:28.200 --> 0:25:32.800 the Epic of Gilgamesh, the oldest known written document. So 0:25:33.480 --> 0:25:36.600 the reason that I included Gilgamesh in the beginning, I'm 0:25:36.600 --> 0:25:41.080 like now calling back to it is that a big 0:25:41.119 --> 0:25:44.760 part of the story is about the quest for immortality. 0:25:45.240 --> 0:25:49.280 So King Gilgamesh's best friend dies and in response, Gilgamesh 0:25:49.400 --> 0:25:54.760 vows to find eternal life. Spoilers he does not. And 0:25:55.080 --> 0:25:57.440 I'm sure between the two of us we can think 0:25:57.520 --> 0:26:01.359 of dozens and dozens more books or movies or poems 0:26:01.480 --> 0:26:05.880 or songs about the search for eternal life. But it's 0:26:05.920 --> 0:26:08.560 not just like one of my favorite books growing up. 0:26:08.640 --> 0:26:14.639 Let's talk Everlasting and for a long time you have 0:26:14.720 --> 0:26:15.680 you read talk ever Lasting? 0:26:15.720 --> 0:26:18.119 Rush. I didn't even know it was a book. I 0:26:18.960 --> 0:26:21.359 thought it was a movie, but I've never seen. 0:26:21.119 --> 0:26:25.280 It, okay, or read it. Basically, it's about this family 0:26:25.440 --> 0:26:28.400